Abstract

Streptococcus pneumoniae and Streptococcus mitis are naso-oropharyngeal commensals that are genetically similar. However, S. pneumoniae is highly pathogenic and a common cause of pneumonia and septicaemia, whereas S. mitis rarely causes disease. We hypothesise that differences in sensitivity to innate immunity may underlie these differences in virulence phenotype. Using multiple strains of S. pneumoniae and S. mitis, we compared their ability to grow in biological fluids and determined their sensitivity to complement and its effect. Overall, S. mitis demonstrated significant susceptibility to complement and complement-mediated neutrophil killing. S. pneumoniae resistance to complement is partially dependent on binding of the immune regulator Factor H by the surface protein, PspC. S. mitis is unable to bind factor H. By inserting pspC of S. pneumoniae into S. mitis, we confirmed that expression of PspC enabled S. mitis to then bind Factor H. Investigation of C3b/iC3b confirmed a decrease in opsonisation. Furthermore, survival in whole human blood of this modified strain showed an increase, when compared to the wild-type strain. These results suggest that an inability to bind factor H might underpin S. mitis sensitivity to opsonisation with complement and neutrophil killing compared to S. pneumoniae, and therefore contribute to the differences in virulence between these two commensal species. The S. pneumoniae surface capsule is an essential virulence factor and modulates interactions between the bacteria and host immune cells. S. mitis has recently been shown to possess a surface capsule, with some identical to S. pneumoniae. Previously it has not been possible to investigate the physical properties of bacterial capsules. Using electron microscopy and newly developed atomic force microscopy techniques, we have investigated the differences in the biomechanical properties of S. mitis and S. pneumoniae capsules. The data show clear differences in the thickness, visible morphology, and physical properties (elasticity and adhesion) between capsules with different chemical structures. In addition, capsules with the same chemical structure expressed on S. mitis and on S. pneumoniae show significant differences in their depth and physical properties between the two species. Overall the data from the thesis demonstrate several important differences in the biological properties of S. mitis and S. pneumoniae that contribute to why the former has low pathogenicity.

Type:

Thesis
(Doctoral)

Title:

Mechanisms of differential virulence between Streptococcus pneumoniae and Streptococcus mitis